Progression from islet autoimmunity to clinical type 1 diabetes is influenced by genetic factors: Results from the prospective TEDDY study - UTU Research Portal

A1 Refereed original research article in a scientific journal

Progression from islet autoimmunity to clinical type 1 diabetes is influenced by genetic factors: Results from the prospective TEDDY study

Authors: Beyerlein A., Bonifacio E., Vehik K., Hippich M., Winkler C., Frohnert B., Steck A., Hagopian W., Krischer J., Lernmark Å., Rewers M., She J., Toppari J., Akolkar B., Rich S., Ziegler A.; TEDDY Study Group

Publisher: BMJ Publishing Group

Publication year: 2019

Journal: Journal of Medical Genetics

Journal name in source: Journal of Medical Genetics

Volume: 56

First page : 602

Last page: 605

eISSN: 1468-6244

DOI: https://doi.org/10.1136/jmedgenet-2018-105532

Abstract

BACKGROUND:

Progression time from islet autoimmunity to clinical type 1 diabetes is highly variable and the extent that genetic factors contribute is unknown.

METHODS:

In 341 islet autoantibody-positive children with the human leucocyte antigen (HLA) DR3/DR4-DQ8 or the HLA DR4-DQ8/DR4-DQ8 genotype from the prospective TEDDY (The Environmental Determinants of Diabetes in the Young) study, we investigated whether a genetic risk score that had previously been shown to predict islet autoimmunity is also associated with disease progression.

RESULTS:

Islet autoantibody-positive children with a genetic risk score in the lowest quartile had a slower progression from single to multiple autoantibodies (p=0.018), from single autoantibodies to diabetes (p=0.004), and by trend from multiple islet autoantibodies to diabetes (p=0.06). In a Cox proportional hazards analysis, faster progression was associated with an increased genetic risk score independently of HLA genotype (HR for progression from multiple autoantibodies to type 1 diabetes, 1.27, 95% CI 1.02 to 1.58 per unit increase), an earlier age of islet autoantibody development (HR, 0.68, 95% CI 0.58 to 0.81 per year increase in age) and female sex (HR, 1.94, 95% CI 1.28 to 2.93).

CONCLUSIONS:

Genetic risk scores may be used to identify islet autoantibody-positive children with high-risk HLA genotypes who have a slow rate of progression to subsequent stages of autoimmunity and type 1 diabetes.